During the last several years this laboratory has continued to be intimately involved in the development of human lymphocyte cell separation procedures, human lymphocyte functional assays, T cell cloning strategies, T cell hybridization and the assessment of T cell surface molecules using monoclonal antibodies that together permit precise analysis of human immune responses in vitro. More recently, our laboratory has begun to utilize DNA-mediated transfer of genes encoding human T cell surface molecules to further explore functional properties of human T cells. The thrust of the current proposal is to bring to bear these newer technologies to analyze the relationship of the function of T cell surface molecules to the cellular interactions important in antigen recognition, T cell triggering and immunoregulation. Recent data from our laboratory and others strongly suggest that many if not all of the already defined surface molecules on human T cells, including the T1, T3, T4, T8 and T11 molecules themselves, as well as recently defined activation antigens, serve as critical structures important in lymphocyte function. Our specific aims are to: (1) further define the heterogeneity of cellular functions contained within the mutually exclusive T4+ and T8+ subsets of mature human T cells. In these studies we will also continue to analyze the T-T, T-B, and T-macrophage cellular imteractions important in the functions of isolated subsets; (2) further define the precise functional role of T4+ and T8+ glycoprotein molecules themselves in antigen recognition and MHC restriction as well as helper and suppressor functions; and (3) further define the functional role of T cell glycoproteins expressed on the majority of human T cells including T1, T3 and T11 antigens. This will involve functional studies to determine the importance of these molecules in T cell triggering, activation and recognition. In many of these studies we should emphasize that we plan to analyze not only freshly isolated populations of human T cells but also IL-2 dependent T cell clones and murine fibroblasts expressing human T cell glycoproteins after DNA mediated transfer of genes encoding these molecules. These studies will be essential to further the understanding of human diseases involving immunodeficiency and/or imbalances in the regulation of T cell function including AIDS, autoimmune states and neoplastic states.